Healthcare‐acquired infections (HAI) impact on patient care and have cost implications for the Australian healthcare system. The management of HAI is exacerbated by rising rates of antimicrobial resistance (AMR). Health‐care workers and a contaminated hospital environment are increasingly implicated in the transmission and persistence of multi‐resistant organisms (MRO), as well as other pathogens, such as Clostridium difficile. This has resulted in a timely focus on a range of HAI prevention actions. Core components include antimicrobial stewardship, to reduce overuse and ensure evidence‐based antimicrobial use; infection prevention strategies, to control MRO – particularly methicillin‐resistant Staphylococcus aureus (MRSA), vancomycin‐resistant Enterococcus spp. (VRE) and, more recently, multi‐resistant Gram‐negative bacteria; enhanced institutional investment in hand hygiene; hospital cleaning and disinfection; and the development of prescribing guidelines and standards of care. AMR surveillance and comparisons of prescribing are useful feedback activities once effectively communicated to end users. Successful implementation of these strategies requires cultural shifts at local hospital level and, to tackle the serious threat posed by AMR, greater co‐ordination at a national level. HAI prevention needs to be multi‐modal, requires broad healthcare collaboration, and the strong support and accountability of all medical staff.